JP2016501235A - Use of Bacopa monnieri extract - Google Patents

Abstract

The present invention generally relates to a method for rapidly improving / enhancing cognitive ability in a human subject comprising administering a Bacopa monnieri extract. [Selection figure] None

Description

  The present invention generally relates to a method for rapidly improving / enhancing cognitive ability comprising the step of administering a Bacopa monnieri extract to a human subject.

  Bacopa monnieri is a perennial herb that grows in wetlands and muddy shores. Bacopa monnieri has been used in traditional Ayurvedic medicine for thousands of years for its anti-amnestic, sedative, memory-enhancing, anti-epileptic, and anti-anxiety effects that it is called to have Yes.

  The inventors are surprised that Bacopa monnieri extract rapidly improves cognitive performance in humans who are mentally stressed, mentally fatigued, and / or who have cognitive impairment I found it.

  In a first aspect, the present invention provides a human who is mentally stressed, mentally fatigued and / or has cognitive impairment comprising administering to a subject a Bacopa monnieri extract Provide a method to rapidly improve / enhance cognitive ability in subjects.

  The extract may be prepared from the stems, leaves and roots of Bacopa monnieri.

The extract may be an alcohol extract, and in one embodiment is an aqueous alcohol extract, such as, for example, an aqueous C ₁ -C ₆ alcohol extract. In one embodiment, the aqueous C ₁ -C ₆ alcohol extract is a 50% (v / v) aqueous alcohol extract. The C ₁ -C ₆ alcohol may be ethanol.

  The extract may comprise at least 55% (w / w) bacoside.

  The extract may be administered to the subject before, during, or after the subject is mentally stressed, mentally fatigued, and / or has cognitive impairment. Typically, the extract is administered to a subject before the subject is mentally stressed, mentally fatigued, and / or has cognitive impairment. In one embodiment, the extract is at least about 15 minutes, at least or about 30 minutes, at least or about 1 hour before the subject is mentally stressed, mentally fatigued, and / or has cognitive impairment. Or at least about 2 hours prior to administration.

  A subject may be mentally stressed, mentally fatigued, and / or have cognitive impairment as a result of experiencing testing, testing, or other activities involving cognition.

  The extract may be administered before the start of testing, testing, or other activities involving cognition.

  The extract is administered at least or about 15 minutes, at least or about 30 minutes, at least or about 1 hour, or at least or about 2 hours before the start of testing, testing, or other activity involving cognition. Also good.

  The extract may be administered in an amount of about 200 mg to about 2.0 g, or about 300 mg to about 1.0 g, or about 320 mg to about 960 mg, or about 320 mg to about 640 mg.

  The extract may be administered in an amount of at least about 320 mg, or in an amount of at least about 640 mg, or in an amount of at least about 960 mg.

  In a second aspect, the present invention relates to a Bacopa monnieri (Bacopa) for rapidly improving / enhancing cognitive ability in a human subject who is mentally stressed, mentally fatigued, and / or who has cognitive impairment. monnieri) provides use of the extract.

In a third aspect, the present invention relates to bacopa in the manufacture of a medicament for rapidly improving / enhancing cognitive ability in human subjects who are mentally stressed, mentally fatigued and / or who have cognitive impairment. Provide the use of Bacopa monnieri extract.
Embodiments of the present invention are described herein by way of example only and with reference to the following drawings.

Screenshot from Purple Multiple Tasking Framework (MTF). Tasks include (clockwise from the left): mental arithmetic, Stroop, memory search, and visual tracking.

  The following are some definitions that may be helpful in understanding the description of the present invention. These are intended to be general definitions, and these terms alone do not limit the scope of the invention in any way and are presented for a better understanding of the following description.

  Throughout this specification, the word “comprises” or variations such as “comprises” or “comprising” unless the context requires otherwise. Implies the inclusion of a specified step or component or integer, or step or component or group of integers, but also implies the exclusion of any other step or component or integer, or step or component or group of integers It is understood not to. Thus, in the context of this specification, the term “comprising” means “including principally, but not necessarily solely”.

  In the context of this specification, the terms “a” and “an” refer to the grammatical object of one or more (ie, at least one) articles. By way of example, “an element” means one element or more than one element.

  In the context of this specification, the term “about” is understood to refer to a range of numbers that one skilled in the art would consider equivalent to the recited value in the context of achieving the same function or result.

  In the context of this specification, references to numbers in the ranges disclosed herein (eg, 1 to 10) refer to all reasonable numbers within that range (eg, 1, 1.1, 2, 3 3.9, 4, 5, 6, 6.5, 7, 8, 9, and 10) are also encompassed, including any reasonable range within the range (eg, 2-8, 1.5 -5.5, and 3.1-4.7), and thus all subranges of all ranges explicitly disclosed herein are explicitly disclosed. These are merely examples of what is specifically intended, and all possible numerical combinations between the lowest and highest values listed are likewise considered expressly stated in this application. Should be.

  As used herein, the term “and / or” means “and” or “or” or both.

  As used herein, the term “extract” refers to an active preparation derived from Bacopa monnieri. “Activity” in the context of the present specification means that the extract can produce the desired effect as disclosed herein. The extract is obtained by an “extraction” process, which treats the plant material with a solvent, liquid or supercritical fluid to dissolve the active preparation and separates it from the remaining unwanted plant material; It is generally understood by those skilled in the art. The extract may be in liquid form (eg, decoction, solution, exudate or tincture) or solid form (eg, powder or granules).

  In the context of the present specification, the term “rapidly” is understood to mean a relatively quick onset of beneficial cognitive effects. The acute effect is different from the relaxed effect, which is an effect that occurs over a longer period of time. One skilled in the art readily understands and recognizes the difference between acute and relaxed effects.

  In the context of this specification, the term “improving / enhancing” with respect to cognitive ability refers to the Bacopa monnieri extract as compared to the cognitive ability of a subject in the absence of Bacopa monnieri extract. Is understood to mean better or better cognitive ability in a subject administered. Improvement / enhancement is assessed by comparing the cognitive ability of a subject in the absence of Bacopa monnieri extract with the cognitive ability of the same subject receiving Bacopa monnieri extract. May be. The improvement / enhancement may be qualitative or quantitative. Improvement / enhancement is at least or about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, It may be 75%, 80%, 85%, 90% or 95%.

  In the context of this specification, the term “cognitive ability” refers to the ability or talent of a subject to perform a task that involves or requires cognition, such as consideration, reasoning, understanding, problem solving and / or decision making. Then it is understood.

  In the context of the present specification, the term “having cognitive impairment” means that the subject has a spirit or problem, especially a subject that involves or requires cognition such as consideration, reasoning, understanding, problem solving and / or decision making. Is understood to mean confronting difficult or complex challenges or problems that may cause mental stress or mental fatigue.

  In the context of this specification, the term “stressed” is understood to mean the pressure or tension associated with discussion, reasoning, understanding, problem solving and / or decision making.

  In the context of this specification, the term “mentally exhausted” is understood to mean fatigue or a feeling of fatigue associated with discussion, reasoning, understanding, problem solving and / or decision making.

  The inventors have identified 2 participants' mood, cardiovascular activity, and performance in cognitive tasks that require mental effort (cognitive demand battery) before and after administration of Bacopa monnieri extract. A double-blind, placebo-controlled study was conducted (Example 1) to examine the acute effects of two doses (320 mg and 640 mg) of extract. We also conducted a double-blind, placebo-controlled trial to reproduce and expand the original laboratory view, with different doses of Bacopa monnieri extracts (Cocomonieri) extracts on cognitive performance and mood effects ( 320 mg, 640 mg, and 960 mg) were also evaluated (Example 2).

  Completion of the cognitive demand battery caused an increased experience of predicted participant stress and fatigue. There was no reduction in either assessment for both doses compared to placebo. This result suggests that Bacopa monnieri does not reduce the experience of experimentally induced stress or fatigue after 1 hour of an assessment that requires significant cognition at the doses evaluated. .

  Assessment of the effect of Bacopa monnieri on cardiovascular activity uses assessment of central and brachial blood pressure, and assessment of arterial wall stiffness (intensity factor; derived from pulse and augmentation pressure) Carried out. No treatment-related effects were observed in relation to blood pressure and arterial wall stiffness. Changes in mood or brain activity caused by ingestion of Bacopa monnieri are monitored for brain activity during the absorption phase using electroencephalography (EEG), with high EEG temporal resolution and relatively good spatial resolution. May be better assessed by first identifying the psychopharmacological effects produced by, and first capturing any acute effects of Bacopa monnieri on brain activity. Near-infrared spectroscopy can also be used to monitor cerebral blood flow and hemodynamics by changes in oxygenated and deoxygenated hemoglobin within the brain region of interest during a cognitive task.

  Following the completion of 6 iterations of the cognitive demand battery, changes from baseline score indicate that 320 mg of extract improved performance in the first, second, and fourth iterations after administration. Suggested. The greatest discrepancy in performance occurred in the fourth iteration, suggesting an optimal effect, probably at the time when participants are expected to reach the maximum level of mental stress and fatigue. Thus, the present invention provides that the Bacopa monnieri extract rapidly improves cognitive ability in humans who are mentally stressed, mentally fatigued, and / or who have cognitive impairment. Based on the discovery by

  In one aspect, the present invention relates to a human subject that is mentally stressed, mentally fatigued, and / or cognitively impaired, comprising a method of administering a Bacopa monnieri extract to a subject. Provide a way to rapidly improve / enhance cognitive skills.

  In another aspect, the present invention provides a Bacopa monnieri for rapidly improving / enhancing cognitive ability in a human subject who is mentally stressed, mentally fatigued, and / or who has cognitive impairment. ) Provide use of the extract.

  In a further aspect, the present invention relates to Bacopa Montnieri in the manufacture of a medicament for rapidly improving / enhancing cognitive ability in human subjects who are mentally stressed, mentally fatigued, and / or who have cognitive impairment. The use of (Bacopa monnieri) extract is provided.

Extracts for use in accordance with the present invention are obtained by single, complex and / or continuous extraction of any available part such as Bacopa monnieri leaves, stems, roots, shoots, seeds and / or florets. It may be an aqueous and / or organic solvent based extract. In one embodiment, the extract is obtained from leaves, roots, and stems. Appropriate extraction steps and suitable solvents and liquids for extraction are known to those skilled in the art. Suitable solvents that may be used in the solvent extraction method include, but are not limited to, water, alcohols, acetone, chlorinated solvents, and ether solvents such as diethyl ether and THF. In some embodiments, the extract is an alcohol extract, particularly an aqueous alcohol extract. Suitable alcohols are well known to those skilled in the art. Typically, the alcohol, such as ethanol is a _C 1 -C ₆ alcohols, such as. In one embodiment, the extract comprises about 10% (v / v) to about 90% (v / v) alcohol, or about 20% (v / v) to about 80% (v / v) alcohol, Or about 30% (v / v) to about 70% (v / v) alcohol, or about 40% (v / v) to about 60% (v / v) alcohol, or about 45% (v / v) ) To about 55% (v / v) alcohol, or an aqueous alcohol mixture comprising about 50% (v / v) alcohol, obtained by extraction of Bacopa monnieri. In one embodiment, the alcohol is ethanol.

  Supercritical fluid extraction using, for example, supercritical nitrogen or carbon dioxide may also be used to obtain an extract according to the present invention.

  Further, for example, to increase or maintain the stability of the extract, to modify or change the physical form of the extract, or to help formulate the extract into a composition for administration to a subject, It will be appreciated by those skilled in the art that the extract of the present invention may be the subject of one or more post-extraction steps. By way of example only, liquid form extracts may be lyophilized to produce solid form extracts.

  In an embodiment of the invention, the extract is at least 15% (w / w), at least 25% (w / w), at least 35% (w / w), at least 45% (w / w), at least 50% (W / w), at least 55% (w / w), at least 65% (w / w), at least 75% (w / w), or at least 85% (w / w) bacoside. In another embodiment, the extract is a 20: 1 to 30: 1 extract or an extract of about 25: 1.

  Commercial extracts that may be used in the present invention are those sold by SOHO Floridas International under the trade name KeenMind®.

  The extract may be administered according to the present invention in the form of a pharmaceutical composition that may comprise one or more pharmaceutically acceptable carriers, excipients or diluents. The composition may be administered by any convenient or suitable route, for example parenteral, oral, or topical route. Typically, the composition is administered by the oral route.

  The pharmaceutical compositions used according to the invention may conveniently be prepared by methods well known in the pharmaceutical art. All methods include combining a Bacopa monnieri extract with one or more pharmaceutically acceptable carriers, diluents and / or excipients. In general, the composition may be prepared by uniformly and intimately combining a Bacopa monnieri extract with a liquid carrier or a finely dispersed solid carrier.

  Examples of pharmaceutically acceptable carriers, diluents, and excipients include demineralized or distilled water; saline solutions; vegetable oils such as peanut oil, safflower oil, olive oil, cottonseed oil, corn oil, and sesame oil Volatile silicones; mineral oils; cellulose derivatives such as methylcellulose, ethylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose or hydroxypropylmethylcellulose; fatty acid esters; polyvinylpyrrolidone; carrageenan; and gums, but are not limited to Absent. Typically, carriers, diluents, and excipients constitute from 5% to 99.9% of the composition weight. Of course, carriers, diluents, and excipients must be tolerated and not harmful to the subject in the sense of being compatible with any other component of the composition.

  Compositions suitable for oral administration may be presented as discrete units, such as gelatin or HPMC capsules, cachets or tablets each containing a predetermined amount of extract.

  When provided in capsule form, the extract is formulated with one or more pharmaceutically acceptable carriers such as starch, lactose, microcrystalline cellulose, silicon dioxide and / or cyclic oligosaccharides such as cyclodextrins. May be. Additional ingredients include lubricants such as magnesium stearate and / or calcium stearate.

  A tablet may be prepared by compression or molding, optionally with one or more accessory ingredients. Compressed tablets can be easily prepared as powders or granules, optionally mixed with a binder, lubricant (eg, magnesium stearate or calcium stearate), inert diluent or surfactant / dispersant in a suitable device. It may be prepared by compressing the extract in fluid form. Molded tablets may be made by molding, in a suitable device, a mixture of the powder extract moistened with an inert liquid diluent. The tablets may optionally be coated, for example with an enteric coating, and may be formulated therein to provide a slow or controlled release of the extract.

  As an alternative, the extract may be administered neat, i.e. in the absence of carriers, excipients and / or diluents.

  The use of Bacopa monnieri extract according to the invention described herein can rapidly increase cognitive performance in human subjects who are mentally stressed, mentally fatigued, and / or who have cognitive impairment. Improve / strengthen. In embodiments of the invention, the improved or enhanced preferred ability is observed and / or achieved within about 15-240 minutes of extract administration. In some embodiments, the improvement or enhancement is within about 30, 45, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330, 360, 390 minutes or about 420 minutes of extract administration. Within and / or achieved.

  In order to obtain improved and / or increased cognitive ability, subject to extract before, during and / or after subject is mentally stressed, mentally fatigued and / or has cognitive impairment It may be administered. In some embodiments, the extract is at least 1 minute, at least 5 minutes, at least 10 minutes, at least 20 minutes, at least, wherein the subject is mentally stressed, mentally fatigued, and / or has cognitive impairment 30 minutes, at least 40 minutes, at least 50 minutes, at least 60 minutes, at least 70 minutes, at least 80 minutes, at least 90 minutes, at least 100 minutes, at least 110 minutes, at least 120 minutes, at least 130 minutes, at least 140 minutes, or at least 150 Dosage before minutes. In another embodiment, the extract is about 5 minutes to about 3 hours before, or about 15 minutes to about 3 hours before the subject is mentally stressed, mentally fatigued, and / or has cognitive impairment, Or about 30 minutes to about 3 hours, or about 1 hour to about 3 hours, or about 2 hours to about 3 hours. In a further embodiment, the extract is up to 1 minute, up to 5 minutes, up to 10 minutes, up to 20 minutes, up to 30 minutes, wherein the subject is mentally stressed, mentally fatigued and / or has cognitive impairment, Maximum 40 minutes Maximum 50 minutes Maximum 60 minutes Maximum 70 minutes Maximum 80 minutes Maximum 90 minutes Maximum 100 minutes Maximum 110 minutes Maximum 120 minutes Maximum 130 minutes Maximum 140 minutes Maximum 150 minutes Maximum 180 minutes Dosage minutes, or up to 210 minutes before.

  A subject may be mentally stressed, mentally fatigued, and / or have cognitive impairment as a result of experiencing testing, testing, or other activities involving cognition. Embodiments of the invention include the test, test, test, test, test, or other activity resulting from administering the extract disclosed herein before, during, or after the test, test, or other activity. Or provide cognitive improvement in other activities. Thus, the methods and uses of the present invention have particular application in subjects being studied, such as high school students, college students, and the like. However, one of ordinary skill in the art will recognize that the methods and uses of the present invention can be applied to subjects that require effort to perform any task involving cognition. For example, the method may have application in a subject in a work environment where the subject is required to complete a cognitively difficult and demanding task in a relatively short time.

  In some embodiments, at least 5 minutes, at least 10 minutes, at least 20 minutes, at least 30 minutes of initiation of a test, test, or other activity involving cognition to obtain improved and / or enhanced cognitive ability At least 40 minutes, at least 50 minutes, at least 60 minutes, at least 70 minutes, at least 80 minutes, at least 90 minutes, at least 100 minutes, at least 110 minutes, at least 120 minutes, at least 130 minutes, at least 140 minutes, or at least 150 minutes before In addition, the extract may be administered. In another embodiment, the extract is about 5 minutes to about 3 hours, or about 15 minutes to about 3 hours, or about 30 minutes to about 3 hours before the start of testing, testing, or other activity involving cognition. It is administered about 1 hour to about 3 hours before, or about 2 hours to about 3 hours before. In further embodiments, the extract may be up to 1 minute, up to 5 minutes, up to 10 minutes, up to 20 minutes, up to 30 minutes, up to 40 minutes, up to 50 minutes of initiation of testing, testing, or other activities involving cognition. Up to 60 minutes, up to 70 minutes, up to 80 minutes, up to 90 minutes, up to 100 minutes, up to 100 minutes, up to 120 minutes, up to 130 minutes, up to 140 minutes, up to 150 minutes, up to 180 minutes, or up to 210 minutes ago To be administered.

  In order to obtain improved and / or enhanced cognitive ability, the extract may be in an amount of about 50 mg to about 5.0 g, or about 100 mg to about 3.0 g, or about 100 mg to about 2.5 g, or An amount of about 200 mg to about 2.0 g, or an amount of about 200 mg to about 1.5 g, or an amount of about 300 mg to about 1.5 g, or an amount of about 400 mg to about 1.5 g, or about 500 mg to about 1. An amount of 5 g, or an amount of about 600 mg to about 1.5 g, or an amount of about 700 mg to about 1.5 g, or an amount of about 800 mg to about 1.5 g, or an amount of about 900 mg to about 1.5 g, or about An amount of 1.0 g to about 1.5 g, or an amount of about 1.1 g to about 1.5 g, or an amount of about 1.2 g to about 1.5 g, or an amount of about 1.3 g to about 1.5 g; Or it may be administered in an amount of about 1.4 g to about 1.5 g.The extract is in an amount of about 300 mg to about 1.4 g, or about 300 mg to about 1.3 g, or about 300 mg to about 1.2 g, or about 300 mg to about 1.1 g, or about 300 mg. To about 1.0 g, or about 300 mg to about 900 mg, or about 300 mg to about 800 mg, or about 300 mg to about 700 mg, or about 300 mg to about 600 mg, or about 300 mg to about 500 mg. Or in an amount of about 300 mg to about 400 mg. The extract may be administered in an amount of about 160 mg to about 960 mg, or about 300 mg to about 750 mg, or about 320 mg to about 640 mg. In one embodiment, the extract is administered in an amount of at least about 120 mg, an amount of at least about 320 mg, an amount of at least about 640 mg, or an amount of at least about 960 mg. In one embodiment, the extract is administered in an amount of about 160 mg, about 320 mg, or about 640 mg, or about 960 mg.

  The extract may be administered as a single dose or, alternatively, as multiple doses sequentially.

  In a further aspect, the present invention relates to Bacopa Montnieri in the manufacture of a medicament for rapidly improving / enhancing cognitive ability in human subjects who are mentally stressed, mentally fatigued, and / or who have cognitive impairment. The use of (Bacopa monnieri) extract is provided.

  The use of Bacopa monnieri extract according to the invention described herein can rapidly increase cognitive performance in human subjects who are mentally stressed, mentally fatigued, and / or who have cognitive impairment. Improve / strengthen. In embodiments of the invention, the improved or enhanced preferred ability is observed and / or achieved within about 15-240 minutes of drug administration. In some embodiments, the improvement or enhancement is within about 30, 45, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330, 360, 390 minutes or within about 420 minutes of drug administration. Observed and / or achieved.

  In some embodiments, at least 5 minutes, at least 10 minutes, at least 20 minutes, at least 30 minutes of initiation of a test, test, or other activity involving cognition to obtain improved and / or enhanced cognitive ability At least 40 minutes, at least 50 minutes, at least 60 minutes, at least 70 minutes, at least 80 minutes, at least 90 minutes, at least 100 minutes, at least 110 minutes, at least 120 minutes, at least 130 minutes, at least 140 minutes, or at least 150 minutes before In addition, a drug may be administered. In another embodiment, the agent is from about 5 minutes to about 3 hours, or from about 15 minutes to about 3 hours, or from about 30 minutes to about 3 hours before the start of a test, test, or other activity involving cognition. Administered before, or from about 1 hour to about 3 hours, or from about 2 hours to about 3 hours. In a further embodiment, the agent may have a duration of up to 1 minute, up to 5 minutes, up to 10 minutes, up to 20 minutes, up to 30 minutes, up to 40 minutes, up to 50 minutes, Up to 60 minutes, up to 70 minutes, up to 80 minutes, up to 90 minutes, up to 100 minutes, up to 110 minutes, up to 120 minutes, up to 130 minutes, up to 140 minutes, up to 150 minutes, up to 180 minutes, or up to 210 minutes before Be administered.

  In one embodiment, to obtain improved and / or enhanced cognitive ability, the agent is an extract in an amount of about 50 mg to about 5.0 g, or an extract in an amount of about 100 mg to about 3.0 g, or Extracts in an amount of about 100 mg to about 2.5 g, or extracts in an amount of about 200 mg to about 2.0 g, or extracts in an amount of about 200 mg to about 1.5 g, or about 300 mg to about 1.5 g Extract in an amount, or extract in an amount of about 400 mg to about 1.5 g, or extract in an amount of about 500 mg to about 1.5 g, or extract in an amount of about 600 mg to about 1.5 g, or about 700 mg Extract in an amount of about 1.5 g, or extract in an amount of about 800 mg to about 1.5 g, or extract in an amount of about 900 mg to about 1.5 g, or about 1.0 g to about 1.5 g Amount of extract, or about 1.1 g to about 1.5 g Or about 1.2 g to about 1.5 g of extract, or about 1.3 g to about 1.5 g of extract, or about 1.4 g to about 1.5 g of extract Comprising things. The drug has an extract amount of about 300 mg to about 1.4 g, or an extract amount of about 300 mg to about 1.3 g, or an extract amount of about 300 mg to about 1.2 g, or an extract amount of about 300 mg to about 1.1 g, Or about 300 mg to about 1.0 g of extract, or about 300 mg to about 900 mg of extract, or about 300 mg to about 800 mg of extract, or about 300 mg to about 700 mg of extract, or about 300 mg to about 600 mg of extract It may be administered in an amount, or an extract amount of about 300 mg to about 500 mg, or an extract amount of about 300 mg to about 400 mg. The medicament may be administered in an amount of about 160 mg to about 960 mg of extract, or about 300 mg to about 750 mg of extract, or about 320 mg to about 640 mg of extract. In one embodiment, the agent is administered in an amount of at least about 120 mg extract, or at least about 320 mg extract, or at least about 640 mg extract, or at least about 960 mg extract. In one embodiment, the agent is administered in an extract amount of about 160 mg, about 320 mg, or about 640 mg, or about 960 mg.

  The drug may be administered as a single dose or, alternatively, as multiple doses sequentially.

  The present invention also includes, individually or collectively, parts, components, and characteristics referred to or shown in the specification of the application, and any two or more of any or all of the parts, components, or characteristics. In general, it can be said to be in all combinations, and when a specific integer having equivalents known in the art to which the present invention pertains is referred to herein, such known equivalents are as if It is considered incorporated herein as if it were individually described.

  The present invention will now be described in more detail with reference to the following examples, which are merely illustrative. The examples are intended to serve to illustrate the present invention and should not be construed as limiting the generality of the disclosure of the description throughout this specification.

  The following clinical trials were conducted to demonstrate the present invention.

Example 1
Methods Participants 18-56 years old (mean ± standard deviation = 25.25 ± 9.30) and 24 healthy individuals with a BMI range of 15.40 to 32.74 kg / m ² (23.48 ± 4.39) Volunteers (4 men and 20 women) were recruited for the study. Participants were restricted from participation based on several self-reported screening criteria, including: smokers, individuals with a history of any psychiatric disorder or neurological disorder, endocrine, gastrointestinal or Individuals with bleeding disorders, individuals with chronic illness and infection, and pregnant or lactating individuals were restricted from participating. Any individual taking any drug or herbal extract was also excluded from participation. On the test day, participants were asked to refrain from alcohol and coffee while only having a light breakfast. The study was approved by the Swinburne University Human Research Ethics Committee and registered with the Australian and New Zealand Clinical Trials Registry (ACTRN 12612000810819).

Treatment and study design A double-blind placebo-controlled crossover design was used in this study. On each test day, participants were inactive placebo, 320 mg KeenMind® (CDR08) Bacopa monnieri (BM) extract, or 640 mg KeenMind® (CDR08) BM extract. Four capsules containing were administered. KeenMind (R) (CDR08) has been standardized for over 55% of all bacosides. Each capsule contained 160 mg BM extract (25: 1) corresponding to 4 g dry herb. The KeenMind® (CDR08) BM extract was prepared from stems, leaves and roots of cultivar BM harvested in West Bengal and extracted with 50% ethanol. Placebo capsules were identical in shape, smell, taste, and weight and were provided in the form of four 160 mg capsules (made of inert plant-based material) per participant per test day. Randomization was performed using a computer-generated randomization program that allowed an equivalent probability assigned to one of the three treatment conditions for each visit.

Cognitive request battery (CDB)
The CDB comprises a “Stress and Mental Fatigue” visual rating scale, two consecutive subtraction tasks (continuous 3 and 7), and a Bakan Rapid Visual Information Processing task, all of which are MS Windows®. ) Was performed on the computer running. Individual issues are described below.

(1) “Stress and mental fatigue” visual analog scale (VAS):
Participants showed their current subjective stress and mental fatigue on a 100 mm visual rating scale line. The left endpoint of this line was labeled “None at all” and the right endpoint was labeled “very”. One minute was given to complete the VAS before and after the CDB.

(2) Continuous 3-subtraction task:
Participants were required to perform mental arithmetic over 2 minutes, three as opposed to predetermined numbers, as accurately and as quickly as possible. A random starting number between 800 and 999 was presented on the computer screen, which was cleared upon entry of the first answer. Three-digit numerical responses were recorded via the provided numeric keypad. This was displayed on the desktop computer monitor. The answer entered by the participant appeared on the screen and was hidden with three stars. The end of each answer is signaled by pressing the “Enter” key, the three stars in the box are cleared, and the next three digits can be entered. The tasks were scored for correct answers.

(3) Continuous 7 subtraction tasks:
Participants were required to complete three tasks with the same setting and duration as the three consecutive tasks. But the only significant difference was that the subtraction of 3 was replaced with the subtraction of 7.

(4) Rapid visual information processing task (RVIP):
Participants were required to monitor a random series of numbers for three consecutive odd or even targets. Numbers were presented at a rate of 100 per minute and 8 correct target strings were presented per minute. Participants responded to detection of the target string by pressing the “Space” bar as quickly as possible. The task was scored by calculating the number of correct target strings identified and the reaction time to correct detection. The task lasted 5 minutes. The total duration of each cycle of CDB (continuous 3, continuous 7, and RVIP) was 10 minutes.

Blood pressure Upper arm blood pressure was calculated with the participant seated following a 5-minute rest period in the morning. All measurements were calculated using an automated sphygmomanometer (Omron, 705IT), designed for business use and validated according to both the European Hypertension Society (EHS) and British Hypertension Society (BHS) protocols. Measurements were completed by skilled research assistants and cardiologists using an appropriately sized cuff. Mean arterial pressure (MAP) was calculated according to the following formula: (2 * DBPθSBP) / 3. Pulse pressure and augmentation pressure coefficient PP and augmentation pressure coefficient were centrally calculated by means of applanation tonometry using a non-invasive device (SphygmoCor; AtCor Medical, Sydney, Australia). Through the mathematical transfer function, SphygmoCor, a range of cardiovascular parameters indicative of arterial stiffness was automatically calculated after deriving the ascending aortic waveform from the radial artery recording. While PP was automatically calculated by subtracting central diastolic pressure from central systolic pressure, the central increasing pressure coefficient was calculated by dividing the increasing pressure by PP and multiplying by 100. All records were completed with participants seated, with palms up and arms on the table. In order to ensure the reliability of the analysis, only records with an operator index greater than 85 were used in the statistical analysis. It has been previously observed that cardiovascular parameters induced by SphygmoCor are related to cognitive ability.

Procedure Each participant should attend a total of 4 sessions (1 practice visit and 3 study visits) conducted at weekly intervals to ensure adequate washout between each acute condition. Was requested. Participants were asked to have a light breakfast (eg, a serving cereal or two toasts at home on each test day) before arriving at the test site. The test was conducted in a dedicated suite in the University Laboratory of Swinburne Center for Human Psychopharmacology. Prior to the first study visit, participants completed three CDB cycles. This was to adjust the practice effect and to become familiar with the test batteries and procedures that would be conducted during the test visit. Practice date data was not included in any analysis.

  Upon arrival at the laboratory, participants completed one cycle of CDB. This was followed by measurements of participants' blood pressure, arterial stiffness, and cerebral blood flow. Prior to dosing, 10-minute CDB and cardiovascular measurements (blood pressure, arterial stiffness, and cerebral blood flow) were completed to establish baseline capability. This was immediately followed by oral intake of the assigned treatment tablet. Participants then waited 2 hours following tablet ingestion (in the meantime participants were instructed to take nothing but water and avoid any intense exercise). After a 2-hour waiting period, participants completed a continuous series of 6 CDB cycles that took approximately 60 minutes. The participants' blood pressure, arterial stiffness, and cerebral blood flow were then measured. The same test procedure was performed at all three test visits.

Data processing and statistics All scores were within the acceptable range for these variables and were therefore subject to parametric analysis. Repeated measures ANOVA were performed for each major variable at 7 time conditions (baseline and 1-6 cycles) and treatment (placebo, 320 mg, and 640 mg) conditions. Therefore, several 3 × 6 repeated measures ANOVA were used to compare differences in change from baseline between the three treatment conditions for CDB variables. Where there was a significant interaction between time and treatment, a paired sample t-test was used to investigate the difference between the ability to follow the treatment. Repeated measures ANOVA were performed for both VAS and cardiovascular measurements at two additional time conditions (baseline and post-treatment) and three treatment conditions (placebo, 320 mg, and 640 mg). Therefore, several 2 × 3 repeated measures ANOVA were used to compare the differences between these variables. All statistical tests were two-sided and α was set to 0.05.

Results Throughout the study, no adverse effects were reported for any of the three treatments. Prior to the cognitive testing study, all data were examined for gender and treatment order effects and did not reveal any significant outcome pattern. The baseline performance scores for CDB (mean and standard error), and the differences from each outcome measure and treatment baseline score are summarized in Table 1 below. Significant time, treatment, and time × therapeutic effects are reported in the text below; for the sake of brevity, no insignificant effects are reported.

Cognitive requirement battery continuous 3
Within 3 consecutive tasks, a significant time × treatment interaction (F 10, ₂₁₀ = 1.89, p <0.05) appeared for the correct number of answers. The change from baseline score in each assessment iteration was compared to placebo for the first iteration, t (21) = 2.05, p = 0.05, 4th within 320 mg BM treatment. During the iteration, t (21) = 2.48, p = 0.02, a significantly better ability was revealed and the tendency towards the same effect was strong during the second iteration, t (21) = 2. 02, p = 0.056. A significant main effect on time ( _{F5, 105} = 6.06, p <0.001) was also observed, with more correct answers throughout the repeated assessment. Over the entire assessment period, changes in the number of incorrect responses were not evident.

7 consecutive
For 7 consecutive abilities, a trend towards time x treatment interaction was observed with an incorrect number of responses (F 10, ₂₁₀ = 1.76, p = 0.07). Investigation of changes from baseline score shows that this trend shows improved performance in the 640 mg BM treatment condition, t (21) = 2.10, compared to the 320 mg BM condition during the first iteration. It was shown to be driven mainly by p <0.05. For the correct number of responses, a main effect of time was also observed (F 5, ₁₀₅ = 4.36, p = 0.001), and the number of correct responses increased throughout the repeated assessment.

RVIP
For the RVIP task, no significant change in performance with treatment or over time was observed.

Visual Analog Scale—Stress and Fatigue Assessment An assessment of participants' stress and fatigue assessment was performed before and after completion of the CDB baseline ability. Over three conditions, battery completion induced an increase in fatigue assessment, evidenced by a significant effect of time, F _1,22 = 7.32, p = 0.013. Following a 2-hour break after ingestion of treatment, a participant assessment of fatigue and stress was again performed before and after completion of the CDB (6 repeats). The completion of this long battery is significant in assessing stress (F _1,22 = 8.74, p <0.01) and fatigue (F _1,22 = 67.30, p <0.001). An increase was induced. The interaction between treatment and time for both stress (F2, ₄₄ = 0.31, p> 0.05) and fatigue ( _F2,44 = 1.74, p> 0.05) is significant. Rather, neither treatment suggested that the stress or fatigue-induced effects of CDB were not diminished. The average score (± SE) of the 4 completions of the visual analog scale is in Table 2 below.

Cardiovascular measurements No significant changes were observed in blood pressure (central and brachial assessment) or augmentation pressure factor between the three treatments. The average cardiovascular assessment (± SE) is in Table 3 below.

Discussion Assessment of change from baseline capacity following placebo, 320 mg BM, and 640 mg BM intakes was performed at 320 mg BM, with the ability of the continuous 3-subtraction test to be the first, second, and fourth after administration. It was clarified that it was improved by repeating. In addition, in the first iteration of the continuous 7 subtraction task, a significantly smaller number of inaccurate answers were made under the 640 mg BM condition compared to the 320 mg BM condition. Completion of the CDB generally increased the participants' assessment of stress and fatigue, and these effects were not diminished by the intake of either BM dose. When measuring cardiovascular function, no significant differences were identified between conditions, and perhaps BM had no apparent acute effect on cardiovascular parameters at the evaluated dose and cardiovascular assessment timeline. It has been suggested.

  Ingestion of a clinical standard dose of BM (320 mg; CDRI08) improved the ability of 3 consecutive in 3 of the first 4 CDB repeats. The improvement from this baseline in correct subtraction numbers was in the range of 2-8 more correct subtractions within the 320 mg BM condition compared to placebo over these 4 iterations. The greatest discrepancy in performance between conditions occurred in the fourth iteration, possibly suggesting the optimal effect of clinical standard doses when participants are expected to reach maximum levels of stress and fatigue .

Example 2
Method Participants Twenty healthy volunteers were selected as described in Example 1. Participants' BMI ranged from 14.8 to 32 kg / m ² (22.84 ± 3.09).

Treatment and Study Design The study was an acute 4 arm randomized double blind placebo controlled crossover design. Participants attended four trial sessions and completed cognitive, mood, and stress assessments before supplementation and after 1, 2, and 4 hours. Participants took each treatment orally immediately after the snack each time. Each treatment was administered after a one week washout period. On each study day, participants were inactive placebo, 320 mg of KeenMind® (CDR08) Bacopa monnieri (BM) extract, or 640 mg of KeenMind® (CDR08) BM extract. Or 6 capsules containing 960 mg of KeenMind® (CDR08) BM extract. KeenMind (R) (CDR08) has been standardized for over 55% of all bacosides. Each capsule contained 160 mg BM extract (25: 1) corresponding to 4 g dry herb. The KeenMind (R) (CDR08) BM extract was prepared from BM stems, leaves and roots of cultivated varieties collected in West Bengal and extracted with 50% ethanol. Placebo capsules were identical in shape, smell, taste, and weight and were provided in the form of four 160 mg capsules (made of inert plant-based material) per participant per test day. Randomization was performed using a computer-generated randomization program that allowed an equivalent probability assigned to one of the four treatment conditions for each visit.

Cognitive Ability The Purple Multitasking Framework (MTF), which includes four tasks, was implemented simultaneously to increase the sense of stress and partition attention resources so that each participant works with the utmost keen ability .

  The Purple MTF (formerly Defined Intensity Stressor Simulator-DISS) battery was developed as a platform for causing acute psychological stress. Previous studies have shown that the ability of the DISS battery, with confidence, causes increased self-assessment of depressed mood and anxiety and triggers stress-related physiological responses. The specific advantage of this system over other experimental stresses (such as simulated speech) is that it can be repeated on numerous occasions, allowing it to be used in crossover design experiments, psychomotor, memory , And to produce a number of results that allow simultaneous assessment of attention ability.

  The platform has been used successfully in several studies that examine the stress-relieving effects of natural products, including herbal extracts and chewing gum. There are further unpublished data showing similar effects.

  Stress can be described in terms of subjective experience and physiological response, the latter involving activation of the hypothalamic-pituitary-adrenal cortex (HPA) axis and / or sympathetic arms of the autonomic nervous system. All three dimensions of stress can be measured in the laboratory.

  The tasks used in the cognitive ability assessment were mental arithmetic task; Stroop task; tracking task; and memory search task. These challenges are illustrated in FIG. All answers were made with external mice. In this case, a 20-minute version of the platform was used and participants were constantly monitored by research staff to increase performance anxiety (social assessment increased stress with confidence).

  Participants were instructed to address all four issues simultaneously by on-screen standard instructions while monitoring a central counter displaying their cumulative aggregate score. The accuracy and speed of the response determined the score, and failure of the response resulted in a negative score. Throughout the battery completion, researchers were placed in the participant's peripheral vision as if they were monitoring capacity throughout.

  Previous studies have shown that the ability of the platform is sensitive to several interventions, which causes increased self-assessment of depressed mood, anxiety, and stress-related physiological responses. To measure mood effects and physiological stress responses of DISS completion and subsequent changes in these effects due to treatment, before and after each battery completion, mood was measured using the Bond-Lader scale and STAI “state” subscale. evaluated.

  Purple MTF is unique among experimental stressors because it is suitable for repeated measurements. It also provided ability measurements for individual tasks and the overall ability score. In general, successful execution of a DISS battery requires concentration and can be viewed as a measure of executive function and working memory ability.

Mental calculation This task requires participants to perform a series of arithmetic (addition) problems. Participants used the right number pad to click with the mouse on the numbers they thought to be in the right column, exited all columns with the sum, and pressed the Done button. Participants were given 10 points for correct answers and 10 points for incorrect answers.

Stroop The Stroop task is a classic psychological test of selective attention and response inhibition. In this exercise, a series of words are presented in different colors (red, blue, yellow, and green). Participants are asked to click one of the four colored blocks on the right side of the task in response to the font color, regardless of the meaning of the word. For example, if the color name “blue” appears in red font, the correct answer is to click on the right “red” colored block. Each correctly identified word is given 10 points, and for each incorrect answer or if it does not answer within the allotted time (“timeout”), 10 points are subtracted.

Memory search A series of memorized characters was presented to participants. The characters disappear after 4 seconds, but can be browsed again by clicking the “Search List” button. A single target character appeared approximately every 10 seconds. Participants were instructed to indicate whether the target character appeared in the original four-character list by clicking the “Yes” or “No” button. Ten points were given for correct answers, 10 points were subtracted for incorrect answers or no answers, and 5 points were subtracted each time the list was searched.

Visual Tracking This task assesses psychomotor ability. A small dot floated outward from the center of the target comprising 5 concentric circles. Participants were instructed to move the dot as far as possible from the center without hitting the edge of the target before clicking the “Reset” button. Each time the dot passes the circle, 2 points are added (up to 10 points), and a penalty of 10 points is imposed every 0.5 seconds from when the dot hits the outer edge until the participant clicks the “Reset” button. It was done.

Mood Mood effects are important for a better understanding of the subjective effects of acute doses of KeenMind®. These assessments can be more reliable than cognitive scores, especially when assessing results obtained with a small number of participants. Participants were evaluated for criteria of stress, fatigue, attention, satisfaction (happiness), and calmness.

  The condition-characteristic anxiety test (STAI) comprises two scales. The “status” (STAI-S) subscale is a widely used means for measuring fluctuating levels of anxiety. The subscale includes 20 different statements (eg, “I am calm”). Participants assessed how strongly they felt for each statement by marking in four stages, from “not at all” to “very”. The “Characteristic” (STAI-T) subscale includes 20 different statements (eg, “Several unimportant thoughts struggle across the mind”). Participants were asked to show how they generally feel on a scale that ranges from "almost no" to "almost always". The scores for both sections of STAI ranged from 20 to 80, with higher scores suggesting greater anxiety. The STAI trait subscale can be used as a screening tool at baseline to detect participants who may have excessive levels of trait anxiety prior to study initiation. The STAI status subscale was subsequently used both before and after the Purple Multiple Tasking Framework at each study visit to measure the acute level of anxiety in response to stressors. A higher score indicates stronger anxiety. At each completion of the stress battery, subtract the factor score before the Purple Multiple Tasking Framework from the factor score after the Purple Multiple Tasking Framework to reduce the mood change caused by the completion of the Purple Multiple Tasking Framework Battery. A single score representing was obtained.

Procedure Each participant should attend a total of 5 sessions (1 practice visit and 4 study visits) conducted at weekly intervals to ensure adequate washout between each acute condition. Was requested. Participants were asked to have a light breakfast (eg, a serving cereal or two toasts at home on each test day) before arriving at the test site. The test was conducted in a dedicated suite in the University Laboratory of Swinburne Center for Human Psychopharmacology. Prior to the first study visit, participants completed a 3-cycle Purple multiple tasking framework. This was to adjust the practice effect and to become familiar with the test batteries and procedures that would be conducted during the test visit. Practice date data was not included in any analysis.

  Participants received four treatments: Treatment 1-placebo; Treatment 2-320 mg KeenMind®, Treatment 3-640 mg KeenMind®, and Treatment 4-960 mg KeenMind®.

Data processing and statistics All variables were within acceptable limits for these variables and were therefore subject to parametric analysis. Repeated measures ANOVA were performed for each major variable. For cognitive variables derived from Purple MTF, repeated measures ANOVA was performed at 4 levels (baseline, 1 hour after baseline) with 4 levels of treatment (placebo 320, 640, and 960 mg Keenmind®). 2 hours and 4 hours). A different 4 × 4 ANOVA was calculated for each cognitive variable. For mood, this is 4 levels of time (baseline, 1 hour, 2 hours, and 4 hours after baseline), 2 levels of task (before and after Purple MTF), and 4 levels of treatment (placebo, 320, 640, And 960 mg of Keenmind®). Where appropriate, paired-sample t-tests were used to investigate differences between treatment abilities.

Results Throughout the study, no adverse effects were reported for any of the three treatments. Prior to the cognitive testing study, all data were examined for gender and treatment order effects and did not reveal any significant outcome pattern.

1. Cognitive Ability (a) Mental Arithmetic Task The most obvious effect compared to placebo was a change at 1 and 4 hours from baseline at the 320 mg dose. There was a significant improvement in response time to this task over these durations.

(B) Stroop task The effects compared to placebo were changes at 1, 2, and 4 hours from baseline at the 320 mg dose. This suggests improved attention at 320 mg compared to placebo.

(C) Follow-up task The most obvious effect compared to placebo was a change at 4 hours from baseline in the 640 mg condition. This suggests improved visual processing and visual-hand coordination.

(D) Memory search task The most obvious effect compared to placebo was the change at 2 hours from baseline at the 960 mg dose and the change at 2 hours from baseline at the 320 mg dose. This suggests improved information processing and working memory due to the 960 and 320 mg doses.

2. Mood (a) Stress Maximum effect was produced 4 hours after administration of 320 mg dose. Overall, there was a predicted stress increase over time due to the task. However, the 320 mg dose alleviated this overall stress increase.

(B) Fatigue feeling There was a significant increase in fatigue feeling throughout the study conditions. This was also predicted due to the heavy test burden imposed on each participant and due to repeated testing over each test day. All doses (320 mg, 640 mg, and 960 mg) of KeenMind (R) alleviated this effect compared to placebo.

(C) Attentiveness There was a decline in attentiveness over each test session. This was also predicted due to the test plan used. The 960 mg dose alleviated this loss of attention and the most prominent effect at 1 hour suggested that even at the highest dose, the effect may not be sustained beyond 1 hour. .

(D) Satisfaction Satisfaction is usually a measure of happiness. Satisfaction subjective reports declined throughout the day each time. The only effect observed was a 960 mg dose compared to placebo, and an improvement was observed 1 hour after baseline.

(E) Calmness There was no improvement in this variable due to any of the treatments.

Conclusion Overall, the data is similar to that shown in Example 1 with a good correspondence between cognitive and subjective mood data and shows a more powerful effect. The results were generally reproduced and the results shown in Example 1 were expanded. Cognitive ability: Compared to placebo conditions: 320 mg dose improved mental arithmetic, Stroop, and memory search tasks; 640 mg dose improved follow-up tasks; 960 mg dose improved memory search work ability. Regarding mood effects: Compared to placebo: 320 mg dose reduced stress experience; 640 mg dose improved fatigue; 960 mg dose improved fatigue and increased attention and satisfaction.

  In general, all doses administered to participants improved and / or enhanced cognitive ability while participants were stressed, mentally fatigued, and / or have cognitive impairment.

  Those skilled in the art will appreciate that the invention described herein is susceptible to variations and modifications other than those specifically described. The present invention is understood to include all such variations and modifications.

  References to any prior publication (or information derived from a prior publication), or any known matter, are referred to herein as prior publications (or information derived from a prior publication) or known matters are involved in this specification. It should not be construed as such, nor is it recognized or endorsed, or any form of suggestion, that forms part of the common sense of the effort-focused field.

Claims (35)

  Rapidly improving cognitive performance in a human subject experiencing mental stress, mental fatigue and / or cognitive impairment comprising administering to a subject a Bacopa monnieri extract / How to strengthen.   2. The method of claim 1, wherein the extract is prepared from Bacopa monnieri stems, leaves, and roots.   The method according to claim 1 or 2, wherein the extract is an alcohol extract.   The method of claim 3, wherein the alcohol extract is an aqueous alcohol extract. The method of claim 4, wherein the aqueous alcohol extract is an aqueous C ₁ -C ₆ alcohol extract. The aqueous _C 1 -C ₆ alcohol extract, an 50% (v / v) aqueous _C 1 -C ₆ alcohol extract The method of claim 5. The 50% (v / v) aqueous _C 1 -C ₆ alcohol extract, an 50% (v / v) aqueous ethanol extract The method of claim 6.   The method according to any one of claims 1 to 7, wherein the extract comprises at least 55% (w / w) bacoside.   9. The extract of any of claims 1-8, wherein the extract is administered to the subject before, during, or after the subject is mentally stressed, mentally fatigued and / or has cognitive impairment. The method according to claim 1.   10. The method of claim 9, wherein the extract is administered to the subject before the subject is mentally stressed, mentally fatigued, and / or has cognitive impairment.   The extract is at least about 15 minutes, or at least or about 30 minutes, or at least or about 1 hour before, the subject is mentally stressed, mentally fatigued, and / or has cognitive impairment; 11. The method of claim 10, wherein the method is administered at least about 2 hours prior.   9. The subject of any of claims 1-8, wherein the subject is mentally stressed, mentally fatigued, and / or has cognitive impairment as a result of experiencing testing, testing, or other activities involving cognition. The method according to one item.   13. The method of claim 12, wherein the extract is administered prior to initiation of testing, testing, or other activity involving cognition.   The extract is administered at least or about 15 minutes, at least or about 30 minutes, at least or about 1 hour, or at least or about 2 hours before the start of testing, testing or other activities involving cognition The method of claim 13.   The extract is administered in an amount of about 200 mg to about 2.0 g, or about 300 mg to about 1.0 g, or about 320 mg to about 960 mg, or about 320 mg to about 640 mg. The method as described in any one of 1-14.   15. The method of any one of claims 1-14, wherein the extract is administered in an amount of at least about 320 mg, or in an amount of at least about 640 mg, or in an amount of at least about 960 mg.   The method according to any one of claims 1 to 16, wherein the extract is administered orally.   Use of Bacopa monnieri extract to rapidly improve / enhance cognitive ability in human subjects experiencing mental stress, mental fatigue and / or cognitive impairment.   Use of Bacopa monnieri extract in the manufacture of a medicament for rapidly improving / enhancing cognitive abilities in human subjects with mental stress, mental fatigue and / or cognitive impairment .   20. Use according to claim 18 or claim 19, wherein the extract is prepared from the stems, leaves and roots of Bacopa monnieri.   21. Use according to any one of claims 18 to 20, wherein the extract is an alcohol extract.   Use according to claim 21, wherein the alcohol extract is a hydroalcoholic extract. The aqueous alcoholic extract is an aqueous C ₁ -C ₆ alcohol extract, use according to claim 22. The aqueous _C 1 -C ₆ alcohol extract, an 50% (v / v) aqueous _C 1 -C ₆ alcohol extract, use according to claim 23. The 50% (v / v) aqueous _C 1 -C ₆ alcohol extract, an 50% (v / v) aqueous ethanol extract, use according to claim 24.   26. Use according to any of claims 18 to 25, wherein the extract comprises at least 55% (w / w) bacoside.   27. The extract or medicament according to any of claims 18 to 26, wherein the extract or medicament is administered to the subject before, during or after the subject is mentally stressed, mentally fatigued and / or has cognitive impairment. Or use as described in paragraph 1.   28. Use according to claim 27, wherein the extract or medicament is administered to a subject before the subject is mentally stressed, mentally fatigued and / or has cognitive impairment.   The extract or drug is applied at least about 15 minutes, or at least or about 30 minutes, or at least or about 1 hour before the subject is mentally stressed, mentally fatigued, and / or has cognitive impairment. 30. Use according to claim 28, administered prior, or at least about 2 hours prior.   27. Any of claims 18-26, wherein the subject is mentally stressed, mentally fatigued, and / or has cognitive impairment as a result of experiencing testing, testing, or other activities involving cognition. Use according to one paragraph.   31. Use according to claim 30, wherein the extract or drug is administered prior to initiation of testing, testing, or other activity involving cognition.   The extract or drug is at least or about 15 minutes before, at least or about 30 minutes, at least or about 1 hour, or at least or about 2 hours before the start of testing, testing, or other activity involving cognition 32. The method of claim 31, wherein the method is administered.   The extract or drug is in an amount of about 200 mg to about 2.0 g of extract, or about 300 mg to about 1.0 g of extract, or about 320 mg to about 960 mg of extract, or about 320 mg to about 640 mg of extract. 33. Use according to any one of claims 18 to 32, which is administered.   34. Use according to any one of claims 18 to 33, wherein the extract or medicament is administered in an extract amount of at least about 320 mg, or an extract amount of at least about 640 mg, or an extract amount of at least about 960 mg.   35. Use according to any one of claims 18 to 34, wherein the extract or medicament is administered orally.